Obesity is a major risk factor underlying the development of metabolic disease and a growing public health concern globally. Strategies to promote skeletal muscle metabolism can be effective to limit ...the progression of metabolic disease. Here, we demonstrate that the levels of the Hippo pathway transcriptional co-activator YAP are decreased in muscle biopsies from obese, insulin-resistant humans and mice. Targeted disruption of Yap in adult skeletal muscle resulted in incomplete oxidation of fatty acids and lipotoxicity. Integrated 'omics analysis from isolated adult muscle nuclei revealed that Yap regulates a transcriptional profile associated with metabolic substrate utilisation. In line with these findings, increasing Yap abundance in the striated muscle of obese (db/db) mice enhanced energy expenditure and attenuated adiposity. Our results demonstrate a vital role for Yap as a mediator of skeletal muscle metabolism. Strategies to enhance Yap activity in skeletal muscle warrant consideration as part of comprehensive approaches to treat metabolic disease.
In the last 5 years, childhood tuberculosis (TB) has received increasing attention from international organisations, national TB programmes and academics. For the first time, a number of different ...groups are developing techniques to estimate the burden of childhood TB. We review the challenges in diagnosing TB in children and the reasons why cases in children can go unreported. We discuss the importance of an accurate understanding of burden for identifying problems in programme delivery, targeting interventions, monitoring trends, setting targets, allocating resources appropriately and providing strong advocacy. We briefly review the estimates produced by new analytical methods, and outline the reasons for recent improvements in our understanding and potential future directions. We conclude that while innovation, collaboration and better data have improved our understanding of the childhood TB burden, it remains substantially incomplete.
Piglet neonatal diarrhoea is an important issue in modern pig production and is linked to increased mortality and poor growth rates, affecting long-term pig health, increasing use of medication and ...cost of production. Saccharomyces cerevisiae var. boulardii (SB) is a probiotic yeast with documented clinical efficacy in the prevention and treatment of diarrhoeal diseases in humans. The objectives of the current study were to evaluate the effect of SB on occurrence and severity of neonatal diarrhoea in piglets, mortality and growth rate. Forty-six litters (606 piglets) were randomly allocated to a control or SB treatment (n=23 per treatment). Within 24 h of farrowing, piglets assigned to the SB treatment received a single oral dose of a paste containing 3.3×109 CFU of SB CNCM I-1079. Piglets from the control litters received a placebo paste. Piglet weight, mortality and diarrhoea were recorded up to day 7 of age. It was shown that numbers of diarrhoea days were significantly correlated with increased mortality rate and reduced weight gain (P<0.05). SB treatment had no effect on growth or mortality in diarrhoeic litters. However, SB-supplemented litters had significantly lower faecal scores, indicating firmer faeces (P<0.01) and fewer numbers of diarrhoeic days (P<0.01) during the 1st week of life. Reduction in the number of diarrhoeic litters compared with the control group was observed following the probiotic administration (P<0.05). These results highlight the detrimental effects of neonatal diarrhoea on pre-weaning performance and suggest that SB, by reducing diarrhoea duration and severity, has the potential of improving enteric health in the early stages of life in pigs.
The most common reasons for revision of unicompartmental knee arthroplasty (UKA) are loosening and pain. Cementless components may reduce the revision rate. The aim of this study was to compare the ...fixation and clinical outcome of cementless and cemented Oxford UKAs. A total of 43 patients were randomised to receive either a cemented or a cementless Oxford UKA and were followed for two years with radiostereometric analysis (RSA), radiographs aligned with the bone-implant interfaces and clinical scores. The femoral components migrated significantly during the first year (mean 0.2 mm) but not during the second. There was no significant difference in the extent of migration between cemented and cementless femoral components in either the first or the second year. In the first year the cementless tibial components subsided significantly more than the cemented components (mean 0.28 mm (sd 0.17) vs. 0.09 mm (sd 0.19 mm)). In the second year, although there was a small amount of subsidence (mean 0.05 mm) there was no significant difference (p = 0.92) between cemented and cementless tibial components. There were no femoral radiolucencies. Tibial radiolucencies were narrow (< 1 mm) and were significantly (p = 0.02) less common with cementless (6 of 21) than cemented (13 of 21) components at two years. There were no complete radiolucencies with cementless components, whereas five of 21 (24%) cemented components had complete radiolucencies. The clinical scores at two years were not significantly different (p = 0.20). As second-year migration is predictive of subsequent loosening, and as radiolucency is suggestive of reduced implant-bone contact, these data suggest that fixation of the cementless components is at least as good as, if not better than, that of cemented devices.
This study has characterized the dominant non-starter
Lactobacillus
species isolated from different sites in a Stilton cheese to establish its diversity, stress-tolerance, anti-microbial activity and ...potential contribution to quality of cheese. Fifty-nine
Lactobacillus
isolates were cultured from the outer crust, blue veins and white core of the cheese and were speciated phenotypically and by 16S rDNA sequence analysis.
Lactobacillus plantarum
was the dominant species detected with only two isolates identified as
Lactobacillus brevis
. Strains were typed by pulse-field gel electrophoresis (PFGE) using the enzyme
Not
I to examine their genomic diversity. Cluster analysis of PFGE patterns produced five major clusters which associated isolates with their sites of isolation within the cheese. One
L. plantarum
isolate from each cheese site was selected and evaluated for salt, acid, relative humidity, and heat tolerance to determine whether stress conditions within the isolation site selected their phenotype.
D
72°C
values were 6, 13, and 17 s for strains from the crust, veins and core, respectively, suggesting strains on the crust may not have been able to survive pasteurization and therefore had been added post-pasteurization. All strains recovered from heat injury within 24–48 h at 4°C. pH values of 3, 3.5, and 4 suppressed growth but strains showed a varying ability to grow at pH 4.5 and 5; isolates from the core (which has the lowest pH) were the most acid-tolerant. All strains grew at 3.5 and 5% salt but were suppressed at 10%; those from the crust (which has a lower water activity) were the most halo-tolerant, growing at 8% salt whereas strains from the core were sensitive to this salt concentration. All 57
L. plantarum
isolates were examined for antimicrobial activity and variable activity against
Lactobacillus pentosus
and other genera was demonstrated; plantaricin EF genes were present in 65% of strains. It was concluded that there are varied phenotypes and genotypes of
Lactobacillus
in a Stilton cheese according to site of isolation. Occurrence of different
L. plantarum
genotypes could contribute to variation in the cheese quality from batch to batch and provides criteria for selecting isolates as potential adjunct cultures.
Campylobacter jejuni and Campylobacter-specific bacteriophage were enumerated from broiler chicken ceca selected from 90 United Kingdom flocks (n = 205). C. jejuni counts in the presence of ...bacteriophage (mean log₁₀ 5.1 CFU/g) were associated with a significant (P < 0.001) reduction compared to samples with Campylobacter alone (mean log₁₀ 6.9 CFU/g).
Waste from dairy production is one of the largest sources of contamination from antimicrobial resistant bacteria (ARB) and genes (ARGs) in many parts of the world. However, studies to date do not ...provide necessary evidence to inform antimicrobial resistance (AMR) countermeasures. We undertook a detailed, interdisciplinary, longitudinal analysis of dairy slurry waste. The slurry contained a population of ARB and ARGs, with resistances to current, historical and never-used on-farm antibiotics; resistances were associated with Gram-negative and Gram-positive bacteria and mobile elements (ISEcp1, Tn916, Tn21-family transposons). Modelling and experimental work suggested that these populations are in dynamic equilibrium, with microbial death balanced by fresh input. Consequently, storing slurry without further waste input for at least 60 days was predicted to reduce ARB spread onto land, with > 99 % reduction in cephalosporin resistant Escherichia coli. The model also indicated that for farms with low antibiotic use, further reductions are unlikely to reduce AMR further. We conclude that the slurry tank is a critical point for measurement and control of AMR, and that actions to limit the spread of AMR from dairy waste should combine responsible antibiotic use, including low total quantity, avoidance of human critical antibiotics, and choosing antibiotics with shorter half-lives, coupled with appropriate slurry storage.
A longitudinal study of bacteriophages and their hosts was carried out at a broiler house that had been identified as having a population of Campylobacter-specific bacteriophages. Cloacal and excreta ...samples were collected from three successive broiler flocks reared in the same barn. Campylobacter jejuni was isolated from each flock, whereas bacteriophages could be isolated from flocks 1 and 2 but were not isolated from flock 3. The bacteriophages isolated from flocks 1 and 2 were closely related to each other in terms of host range, morphology, genome size, and genetic content. All Campylobacter isolates from flock 1 were genotypically indistinguishable by pulsed-field gel electrophoresis (PFGE). PFGE and multilocus sequence typing indicated that this C. jejuni type was maintained from flock 1 to flock 2 but was largely superseded by three genetically distinct C. jejuni types insensitive to the resident bacteriophages. All isolates from the third batch of birds were insensitive to bacteriophages and genotypically distinct. These results are significant because this is the first study of an environmental population of C. jejuni bacteriophages and their influence on the Campylobacter populations of broiler house chickens. The role of developing bacteriophage resistance was investigated as this is a possible obstacle to the use of bacteriophage therapy to reduce the numbers of campylobacters in chickens. In this broiler house succession was largely due to incursion of new genotypes rather than to de novo development of resistance.
PDF
